Rethinking TB vaccines

As researchers consider who might benefit most from the next wave of tuberculosis (TB) vaccines, some argue that we're not doing enough with the vaccine we already have.

The disappointing results of the first infant TB vaccine tested for efficacy in 40 years were published in February 2013, but new research suggests that while babies might be easier to reach, given existing childhood vaccination programmes, new vaccines will be more cost-effective if geared towards teens and adults.

The findings by the London School of Tropical Medicine are based on mathematical modelling that compared the cost-effectiveness of potential TB vaccines in the top 22 countries with the highest burden of TB, as listed by the World Health Organization (WHO), including South Africa, India and China, which account for 82 percent of all TB cases globally.

Dr Gwen Knight and colleagues used information like the number of new TB cases recorded annually, population projections, and TB mortality. Where available, they also factored in TB treatment and vaccine delivery costs. Finally, they created various scenarios based on projections of, for instance, how well a future vaccine might protect people from active TB, and how long this protection would last.

Knight's preliminary results were presented at the TB Vaccines Third Global Forum in Cape Town. They indicate that in most scenarios, TB vaccines given to teens and adults were about seven times cheaper than those administered to infants. The most cost-effective TB vaccine would be designed for adults and teens, and would confer 80 percent protection on recipients - a high level of protection compared to most vaccines today.

The options in terms of cost-effectiveness

The cost per Disability Adjusted Life Year (DALY) for a vaccine for adults and teens could be as little as 85 US cents, making it comparable to the lowest prices for the rotavirus and human papillomavirus (HPV) vaccines. An infant TB vaccine conferring 50 percent protection for five years could cost as much as US$42,617 per DALY.

Vaccines for older people were modelled as much more effective in reducing TB cases, with deaths occurring at an infection level largely determined by the transmission dynamics within the group. For example, a vaccine offering life-long protection against active TB would avert almost eight times as many new cases as a TB vaccine given to babies.

The model may be important in helping researchers prioritize TB vaccine candidates and selecting groups to include in future clinical trials. "Previous modelling has shown that the global TB burden is unlikely to be controlled without new TB vaccines," Knight told IRIN. "What we didn't know is whether these vaccines would be economically valid, and what type of vaccine should be an economic priority in relation to others."

In the absence of a TB vaccine, Knight and her team projected that as many as 19 million people would die from the disease between 2024 and 2050.

Making the most of what we have

The world relies on the Bacille Calmette-Guérin (BCG) TB vaccine, developed almost 100 years ago. Given at birth, BCG's protective effect wanes as children grow to adulthood, but the vaccine has seldom been considered a candidate for global adult or teen vaccination programmes after poor results in trials.

"While drugs have had a clinical impact, they have failed to control the epidemic - that's why we need vaccines and other tools"

Now there are growing moves in the vaccine community to move away from approaches based solely on infant immunization and to begin developing policies on immunizing adolescents and adults. Adolescents may also be a prime target for re-vaccination with the BCG TB vaccine, according to Christopher Dye, director of health information in the Office of HIV/AIDS, Tuberculosis, Malaria and Neglected Tropical Diseases at WHO.

Dye says the world could do more with the only available TB vaccine in its arsenal. Citing examples from the United Kingdom and Norway, he presented instances in which adult BCG vaccination campaigns in the 1950s and 1960s had not only shown the vaccine to be as much as 80 percent protective, but that it had also reduced new TB cases by 20 percent.

"If those results were obtained today with a TB vaccine, they would be the subject of worldwide acclaim, and they form the basis of my claim that we don't do enough with BCG," he told IRIN.

In their search for a cure-all for TB epidemics, policymakers at the time may have dismissed results too readily. "The interpretation was pretty pessimistic," he said. "In my reading, this was a search for a panacea and when that was not the result obtained, the results were pushed aside." Disappointing results from India and Malawi could be explained by the presence of other tropical bacterial infections that could reduce BCG's effectiveness.

Rethinking vaccines, rethinking TB control

Vaccinating teens and adults might also make sense in places like South Africa, where data collected in the Cape Town area in 2010 shows that people between the ages of 16 and 35 experience elevated risks of TB infection when compared to children and older adults.

"Children between the ages of five and ten are extremely resistant to developing active TB, but then become at risk when they move into adolescence," Dye told IRIN. "Where possible, they need to be re-protected."

He said adolescent BCG vaccination could easily be added to existing campaigns in countries where girls and, in some instances, boys, are vaccinated against HPV before they become sexually active.

Using mathematical models, Dye proposed that repeated mass vaccination campaigns to protect people as infants, and again as teens or young adults, could cut the annual number of new TB cases in South Africa by 50 percent over a 30-year period. In combination with improved case management and preventative TB therapy for people living with HIV, the models projected that revaccination with BCG could cut TB incidence by more than 90 percent by 2050.

"With all of these intense efforts put into TB control through treatment, the impact at the clinical level has been profound, but the trajectory of the TB epidemic has been [more or less flat]," he told IRIN. "It's clear from analysis that while drugs have had a clinical impact, they have failed to control the epidemic - that's why we need vaccines and other tools."

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